crossing96/oncoscreening huggingface dataset:
Seeking a standard for adequate pathologic lymph node staging in primary bladder carcinoma.	The purposes of this study are to evaluate the adequacy of pathologic lymph node (LN) staging in radical cystectomy specimens from patients with urothelial carcinoma of the bladder and to analyze the frequency of LN metastases among different anatomic regions. All radical cystectomies performed for primary urothelial bladder cancer over a 5-year period (January 2007-September 2012) at a single institution were reviewed. Particular attention was paid to the total number of LNs examined, the number and location of LNs with metastases (positive LNs), and the presence or absence of extranodal tumor extension and/or lymphovascular invasion in the cystectomy specimen. Results and data were analyzed with Origin 6.0 and Microsoft Office Excel 2007 software. A total of 248 radical cystectomies with 8,432 LNs were reviewed. A total of 60 (24 %) cases, with 274 positive LNs out of the 1,982 total (13.8 %), were identified with a male to female ratio of 6.5:1 (52 male, 8 female patients). The average number of LNs examined in each case was 33.0 ± 20.9 (range 5-112). The average number of positive LNs identified in each case was 4.5 ± 4.8 (range 1-26). Among all of the LNs, the hypogastric/obturator (internal iliac) LNs were the most commonly submitted (35.2 %) and also yielded the highest number of positive LNs (46.0 %). On average, for cases staged pN1 and pN2, there was one positive LN per 17.8 and 8.9 LNs examined from the primary drainage LNs, respectively. For pN3 cases, one out of 4.4 secondary drainage LNs was found to be positive. Similarly, one out of 4.0 distant LNs was found to be positive in cases with pM1 staging. Our study suggests that, on average, 23 LNs (including 18 primary drainage LNs and five secondary drainage LNs) should be submitted for optimal pN staging. For adequate pM1 staging, an average of four distal LNs should be evaluated. In total, an average of 27 LNs (23 for pN staging and 4 for pM staging) should be examined in radical cystectomy specimens. We also propose to stratify the number of positive LNs according to the drainage area.	bladder
A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer.	PURPOSE: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80 mg in 50 mL) delivered with the novel Combat BRS® system at a temperature of 43 °C for 60 min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. RESULTS: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. CONCLUSIONS: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.	bladder
Diagnostic evaluation of urinary angiogenin (ANG) and clusterin (CLU) as biomarker for bladder cancer.	Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n = 50), benign (n = 20) and healthy (n = 20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.	bladder
Bladder cancer invasion predictability based on preoperative neutrophil-lymphocyte ratio.	An increased pretreatment neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis in colorectal, gastric, and ovarian cancer; malignant mesothelioma; and renal cell carcinoma. The present study aims to define the predictive value of preoperative peripheral blood count NLR in non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease (MIBC) patients. There were in total 291 patients, 241 males and 50 females. Out of these, 156 male and 36 female patients were in the NMIBC group and 85 male and 14 female patients in the MIBC group. In the NMIBC group, 172 patients had low-grade and 20 high-grade papillary urothelial carcinoma. The mean age of the patients in the NMIBC group was 64 ± 13, ranging from 27 to 97. The mean age of the patients in MIBC group was 70.5 ± 10, ranging from 27 to 95. A statistically significant relation between patient ages and tumor invasiveness was determined (p = 0.023, 95 % confidence interval (CI) 63.3-66.7). The mean tumor size of the NMIBC group was 2.1 ± 1.09 (cm) (range 0.5-8), and of MIBC group 3.6 ± 1.5 (cm) (range 0.8-9). There was a statistically significant relation between the tumor size and invasiveness (p = 0.002, 95 % CI 2.8-4.4). In the NIMBC group, 149 (77.6 %) of them have NLR ≤ 2.5 and 43 (22.4 %) have NLR > 2.5. Also, in MIBC, 67 (67.7 %) of them have NLR ≤ 2.5 and 32 (32.3 %) have NLR > 2.5. The mean NLR in the NMIBC group was 2.4 ± 0.1 (range 0.08-6.49, 95 % CI 1.52-2.71) and in the MIBC 2.9 ± 0.2 (range 0.08-16.72, 95 % CI 1.67-2.97). In terms of NLR, there was a statistically significant difference between the NMIBC and MIBC groups (p = 0.028). Platelet-lymphocyte ratio (PLR) of the two groups was also analyzed. The PLR of the NMIBC group was 12.8 ± 15.1 (range 3.38-19.1) and of the MIBC 13.6 ± 8.78 (range 0.18-63), yet there was not any statistically significant difference (p = 0.810, 95 % CI 11.4-14.8) (Table 1). The correlation tests revealed a positive correlation between the age (r = 0.144, p = 0.024), tumor size (r = 0.193, p = 0.02), and tumor invasiveness NLR (r = 0.138, p = 0.031). NLR can be used to determine tumor invasiveness as a cost-effective, common, and simple biomarker in bladder cancer (BC).	bladder
Impact of EZH2 polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic features.	BACKGROUND: The gene EZH2, the polycomb group protein enhancer of zeste 2, encodes a transcriptional repressor that also serves as a histone methyltransferase that is associated with progression to more advanced disease in a variety of malignancies. EZH2 expression level in urothelial cell carcinoma (UCC) is highly correlated with tumor aggressiveness, but it has not been determined if specific EZH2 genetic variants are associated with UCC risk. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with UCC susceptibility and its clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: A total of 233 UCC patients and 552 cancer-free controls, all of whom were from Taiwan, were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, we found that individuals carrying at least one C allele at EZH2 rs6950683 had a lower risk of developing UCC than did major allele carriers. The CCCA or TGTA haplotype among the four EZH2 sites was also associated with a reduced risk of UCC. Furthermore, UCC patients who carried at least one G allele at rs2302427 had a lower invasive tumor stage than did patients carrying the major allele. CONCLUSIONS: The rs6950683 SNPs of EZH2 might contribute to the prediction of UCC susceptibility. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of UCC in Taiwan.	bladder
Simultaneous multi-analyte urinary protein assay for bladder cancer detection.	BACKGROUND: The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of a myriad of clinical assays. Here, we tested the performance of a new, multiplex protein array platform to quantitate three bladder cancer-associated proteins in urine samples. The following analytes, interleukin 8 (IL8), matrix metallopeptidase 9 (MMP9), and vascular endothelial growth factor A (VEGFA) were monitored using Q-plex, a customized multiplex ELISA system from Quansys Biosciences, and individual target commercial ELISA kits. The performance of the two approaches was compared by evaluating the diagnostic accuracy of the biomarker assays in samples from a cohort of 73 subjects of known bladder cancer status. RESULTS: The combination biomarker panel analyses revealed an AUROC value of 0.9476 for the Q-plex assay, and 0.9119 for the combination of the single-target ELISA assays. The Q-plex assay achieved an overall diagnostic sensitivity of 0.93 and specificity of 0.81, and the individual target ELISA assays achieved an overall sensitivity of 0.77 and specificity of 0.91. CONCLUSION: Based on these encouraging preliminary data, we believe that the Q-Plex technology is a viable platform that can be exploited as an efficient, highly accurate tool to quantitate multiplex panels of diagnostic proteins in biologic specimens.	bladder
Health-related quality of life after radical cystectomy and neobladder reconstruction in women: impact of voiding and continence status.	OBJECTIVES: To assess health-related quality of life, and the impact of night-time incontinence and chronic urinary retention on health-related quality of life in women with bladder cancer after radical cystectomy and orthotopic neobladder. METHODS: The study included 74 women who underwent radical cystectomy and orthotopic neobladder, and completed 1 year of follow up. Health-related quality of life was evaluated using the questionnaires of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire and the Functional Assessment of Cancer Therapy bladder cancer-specific form. Health-related quality of life was compared with an age-matched control group. The impact of night-time incontinence and chronic urinary retention on health-related quality of life was assessed. RESULTS: The study group included 18 completely continent patients with spontaneous voiding, 29 with night-time incontinence and 27 with chronic urinary retention. The study group was statistically significantly lower in all domains of health-related quality of life than the control group. In all domains of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire and Functional Assessment of Cancer Therapy bladder cancer-specific form, completely continent women were comparable with those with chronic urinary retention. Women with night-time incontinence had a significantly worse health-related quality of life than completely continent women, shown by the mean global health score (P = 0.038), social functioning score (P = 0.012), pain European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire score (P = 0.04), and functional well-being Functional Assessment of Cancer Therapy bladder cancer-specific form (P = 0.049) score. CONCLUSIONS: After radical cystectomy and orthotopic neobladder in women, health-related quality of life is lower than that of the normal population. Night-time incontinence has a negative impact on social life and most domains of health-related quality of life. Thus, night-time incontinence has a higher social impact than chronic urinary retention.	bladder
Gender-specific outcomes of bladder cancer patients: a stage-specific analysis in a contemporary, homogenous radical cystectomy cohort.	INTRODUCTION: Controversial findings regarding gender-specific oncological outcomes of urothelial carcinoma of the bladder (UCB) have recently been reported. The aim of this study was to analyze gender-specific outcomes using a stage-adjusted approach in a homogenous, contemporary radical cystectomy (RC) cohort. MATERIAL AND METHODS: We prospectively collected data of 517 UCB patients treated with RC and pelvic lymphadenectomy without neoadjuvant chemotherapy at our institution between 1996 and 2010. Stage-adjusted uni- and multivariable Cox regression models analyzed the association of gender with disease recurrence, cancer-specific mortality and overall survival. RESULTS: In total, 398 (77%) patients were male and 119 (23%) were female. Compared to men, women were more likely to have advanced tumor stages (p = 0.017), nodal metastasis (p = 0.047) and received more frequently adjuvant chemotherapy (p = 0.009). At a median follow-up of 44 months, there was no statistical difference in disease recurrence, cancer-specific mortality and overall survival between both genders when analyzed as a group. In stage-adjusted analyses, only women with non-invasive UCB were more likely to die of UCB compared to the male counterparts (p = 0.013). In gender-specific multivariable analyses that adjusted for standard clinico-pathologic features, pathologic tumor stage was an independent predictor for disease recurrence (p-values ≤0.047) and cancer-specific mortality (p-values ≤0.049), respectively. CONCLUSION: Women present with more aggressive tumor biologic features at RC, however this did not translate into inferior outcomes compared to men in stage-specific analyses in our cohort. Tumor stage is the most important factor influencing the course of disease in both genders. Validation of our findings is warranted in a larger cohort.	bladder
Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy.	BACKGROUND: Whether the commonly used bacillus Calmette-Guérin (BCG) strains Connaught and Tice confer different treatment responses in non-muscle-invasive bladder cancer (NMIBC) is unknown. OBJECTIVES: To compare clinical efficacy, immunogenicity, and genetics of BCG Connaught and Tice. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized single-institution trial with treatment of 142 high-risk NMIBC patients with BCG Connaught or Tice. INTERVENTION: Patients were randomized to receive six instillations of BCG Connaught or Tice. For experimental studies, BCG strains were compared in C57Bl/6 mice. Bladders and lymphoid tissues were analyzed by cytometry and the latter cultivated to detect live BCG. BCG genomic DNA was sequenced and compared with reference genomes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence-free survival was the primary end point of the clinical study. The Kaplan-Meier estimator was used for estimating survival and time-to-event end points. Nonparametric tests served for the analysis of the in vivo results. RESULTS AND LIMITATIONS: Treatment with BCG Connaught conferred significantly greater 5-yr recurrence-free survival compared with treatment with BCG Tice (p=0.0108). Comparable numbers of patients experienced BCG therapy-related side effects in each treatment group (p=0.09). In mice, BCG Connaught induced stronger T-helper cell 1-biased responses, greater priming of BCG-specific CD8(+) T cells, and more robust T-cell recruitment to the bladder than BCG Tice. Genome sequencing of the BCG strains revealed candidate genes potentially involved in the differential clinical responses. CONCLUSIONS: BCG strain may have an impact on treatment outcome in NMIBC immunotherapy. PATIENT SUMMARY: We compared the efficacy of two commonly used bacillus Calmette-Guérin (BCG) strains for the treatment of NMIBC and found that treatment with BCG Connaught prevented recurrences more efficiently than BCG Tice. Comparison of the immunogenicity of the two strains in mice indicated superior immunogenicity of BCG Connaught. We also identified genetic differences that may explain the differential efficacy of the Connaught and Tice BCG strains. TRIAL REGISTRATION: NCT00003779.	bladder
[Molecular lymph node staging in prostate and bladder cancer].	A positive lymph node status is a major prognostic factor for tumor recurrence and mortality following radical prostatectomy in prostate cancer patients or radical cystectomy in bladder cancer patients. However, despite having histopathologic negative lymph nodes, a substantial proportion of patient suffers from tumor recurrence within a few years after the operation. Tumor recurrence in node-negative patients may result from hematogeneous or lymphatic metastatic spread which remains undetected by standard clinical or histopathologic examinations. Molecular lymph node analysis is a potential method for detection of lymph node metastases with higher sensitivity and for prognostic risk stratification of patients with histopathologic negative lymph nodes.	bladder
Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients.	Epigenome-wide studies of DNA methylation using blood-derived DNA from cancer patients are complicated by the heterogeneity of cell types within blood and the associated cell lineage specification of DNA methylation signatures. Here, we applied a novel set of analytic approaches to assess the association between cancer case-status and DNA methylation adjusted for leukocyte variation using blood specimens from three case-control cancer studies (bladder: 223 cases, 205 controls; head and neck: 92 cases, 92 controls; and ovarian: 131 cases, 274 controls). Using previously published data on leukocyte-specific CpG loci and a recently described approach to deconvolute subject-specific blood composition, we performed an epigenome-wide analysis to examine the association between blood-based DNA methylation patterns and each of the three aforementioned solid tumor types adjusted for cellular heterogeneity in blood. After adjusting for leukocyte profile in our epigenome-wide analysis, the omnibus association between case-status and methylation was significant for all three studies (bladder cancer: P = 0.047; HNSCC: P = 0.013; ovarian cancer: P = 0.0002). Subsequent analyses revealed that CpG sites associated with cancer were enriched for transcription factor binding motifs involved with cancer-associated pathways. These results support the existence of cancer-associated DNA methylation profiles in the blood of solid tumor patients that are independent of alterations in normal leukocyte distributions. Adoption of the methods developed here will make it feasible to rigorously assess the influence of variability of normal leukocyte profiles when investigating cancer related changes in blood-based epigenome-wide association studies.	bladder
Thermal dosimetry characteristics of deep regional heating of non-muscle invasive bladder cancer.	PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue. MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used to calculate thermal dose and evaluate treatment. Anatomical characteristics were examined for possible correlations with heating. RESULTS: Combined with BSD-2000 standard treatment planning and patient feedback, real-time temperature monitoring allowed thermal steering of heat sufficient to attain the prescribed thermal dose to bladder tissue within patient tolerance in 91.6% of treatments. Mean treatment time for bladder tissue >40 °C was 61.9 ± 11.4 min and mean thermal dose was 21.3 ± 16.5 CEM43. Average thermal doses obtained in normal tissues were 1.6 ± 1.2 CEM43 for the rectum and 0.8 ± 1.3 CEM43 in superficial normal tissues. No significant correlation was seen between patient anatomical characteristics and thermal dose achieved in bladder tissue. CONCLUSIONS: This study demonstrates that a hyperthermia prescription of 42° ± 2 °C for 40-60 min can be delivered safely to bladder tissue with external radiofrequency phased array applicators for a typical range of patient sizes. Using the available thermometry and treatment planning, the BSD-2000 hyperthermia system was shown to be an effective method of focusing heat regionally around the bladder with good patient tolerance.	bladder
Bacillus Calmette-Guerin and bladder cancer: helpful packaging.	There are no randomised controlled trials comparing the BCG RIVM strain (BCG-medac) versus the BCG Connaught strain (Immucyst), but the packaging of BCG-medac is far more complete than that of immucyst.	bladder
Tetrachloroethylene exposure and bladder cancer risk: a meta-analysis of dry-cleaning-worker studies.	"BACKGROUND: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as ""probably carcinogenic to humans"" based on limited evidence of an increased risk of bladder cancer in dry cleaners. OBJECTIVES: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry. METHODS: Random-effects meta-analyses were carried out separately for occupational exposure to tetrachloroethylene and employment as a dry cleaner. We qualitatively summarized exposure-response data because of the limited number of studies available. RESULTS: The meta-relative risk (mRR) among tetrachloroethylene-exposed workers was 1.08 (95% CI: 0.82, 1.42; three studies; 463 exposed cases). For employment as a dry cleaner, the overall mRR was 1.47 (95% CI: 1.16, 1.85; seven studies; 139 exposed cases), and for smoking-adjusted studies, the mRR was 1.50 (95% CI: 0.80, 2.84; 4 case-control studies). CONCLUSIONS: Our meta-analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case-control studies, and some evidence for an exposure-response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because it is the primary solvent used and it is the only chemical commonly used by dry cleaners that is currently identified as a potential bladder carcinogen. Relatively crude approaches in exposure assessment in the studies of ""tetrachloroethylene-exposed workers"" may have attenuated the relative risks."	bladder